Maryse de la Giroday 6-week course SFU Liberal Arts & Adults 55+ program

Bioelectronics, Medical Imaging and Our Bodies

Week 6: Growing organs (regenerative medicine) and human-on-a-chip

Maryse de la Giroday6-week course

SFU Liberal Arts & Adults 55+ program

3D Printing of biological tissue (2011)

• http://channel.nationalgeographic.com/channel/explorer/videos/the-human-cell-printer/

Cornell University’s bioengineered ear 2013 (1 of 7)

• To make the ears, Bonassar and colleagues started with a digitized 3-D image of a human subject’s ear and converted the image into a digitized “solid” ear using a 3-D printer to assemble a mold.


• They injected the mold with collagen derived from rat tails, and then added 250 million cartilage cells from the ears of cows. This Cornell-developed, high-density gel is similar to the consistency of Jell-O when the mold is removed. The collagen served as a scaffold upon which cartilage could grow.


• The process is also fast, Bonassar added: “It takes half a day to design the mold, a day or so to print it, 30 minutes to inject the gel, and we can remove the ear 15 minutes later. We trim the ear and then let it culture for several days in nourishing cell culture media before it is implanted.” [implanted?]


• Bonassar and [Jason] Spector have been collaborating on bioengineered human replacement parts since 2007

• The researchers specifically work on replacement human structures that are primarily made of cartilage — joints, trachea, spine, nose — because cartilage does not need to be vascularized with a blood supply in order to survive.


• They are now looking at ways to expand populations of human ear cartilage cells in the laboratory so that these cells can be used in the mold, instead of cow cartilage.

• “Using human cells, specifically those from the same patient, would reduce any possibility of rejection,” Spector said.


• He added that the best time to implant a bioengineered ear on a child would be when they are about 5 or 6 years old. At that age, ears are 80 percent of their adult size.

• If all future safety and efficacy tests work out, it might be possible to try the first human implant of a Cornell bioengineered ear in as little as three years, Spector said..


• http://www.frogheart.ca/?p=9310 (Feb. 2013)• Paper:– Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL,

et al. (2013) High-Fidelity Tissue Engineering of Patient-Specific Auricles for Reconstruction of Pediatric Microtia and Other Auricular Deformities. PLoS ONE 8(2): e56506. doi:10.1371/journal.pone.0056506 [open access: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0056506]

http://www.frogheart.ca/?p=9310

2011 vs 2013 bioengineered ears at Cornell

• What is the difference?

Beyene and the synthetic trachea (1 of 6)

• Andemariam Teklesenbet Beyene• Synthetic trachea transplant 2011• http://www.frogheart.ca/?p=4078• Student in Iceland, flown to Sweden for

transplant by surgeon, Paolo Macchiarini, who has a double appt. Karolinska Institute in Sweden and University College in London, UK



• Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK),

• created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient.


• In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation


• Seifalian & associates manufactured a full size y-shaped trachea scaffold

• Scaffold was built using a novel porous nanocomposite polymer

• The composite has millions of little holes (pores), providing a place for the patient’s stem cells to grow roots.


• The team cut strips of the novel nanocomposite polymer and wrapped them around the glass mold creating to create cartilage rings that confer structural strength to the trachea

• Then off to Karolinska where stem cells are harvested and grown in a bioreactor

Beyene and synthetic trachea (6 of 6)

• During a 12-hour operation Professor Macchiarini removed all of the tumour and the diseased windpipe and replaced it with the tailor-made replica [now covered with tissue grown from the patient's bone marrow tricked into growing like cells found in a trachea

Contrast ear story and trachea story

• Scan of ear?• CT scan of trachea• ‘Hybrid’ scaffolding (hydrogel and extracellular

matrix [cows] and collagen from rat tails)• Nanocomposite scaffolding• Tissue engineering generally requires

scaffolding

Regenerating a finger and the extracellular matrix (1 of 4)

• http://www.youtube.com/watch?v=gwR8rEcVu7c

• Stem cells may be needed for regrowth, e.g., stem cells in nail bed may be necessary (at this time) for regenerating fingers (http://www.livescience.com/37380-nail-cells-regenerate-lost-fingers.html)

http://www.youtube.com/watch?v=gwR8rEcVu7c

http://www.youtube.com/watch?v=gwR8rEcVu7c

http://www.livescience.com/37380-nail-cells-regenerate-lost-fingers.html

http://www.livescience.com/37380-nail-cells-regenerate-lost-fingers.html


• March 2008 article (Wyatt Anderson) (http://www.cbsnews.com/news/medicines-cutting-edge-re-growing-organs/)

• In 2005, Lee Spievack sliced off the tip of his finger in the propeller of a hobby shop airplane

http://www.cbsnews.com/news/medicines-cutting-edge-re-growing-organs/



• Spievack's brother, Alan, a medical research scientist, sent him a special powder and told him to sprinkle it on the wound.

• "I powdered it on until it was covered," Spievack recalled.

• To his astonishment, every bit of his fingertip grew back.

• "Your finger grew back?”, • "flesh, blood, vessels and nail?“• "Four weeks," he answered.


• Alan worked with Steven Badylak of the University of Pittsburgh's McGowan Institute of Regenerative Medicine

• The special powder was made up extracellular matrix: made from pig bladders. It is a mix of protein and connective tissue surgeons often use to repair tendons and it holds some of the secrets behind the emerging new science of regenerative medicine.

• "It tells the body, start that process of tissue regrowth," said Badylak.

http://www.mirm.pitt.edu/

http://www.mirm.pitt.edu/

Regeneration and money (1 of 4)

• In a [2008] clinical trial at Thomas Jefferson Hospital in Philadelphia, Dr. Patrick Shenot performed a bladder transplant with an organ built with the patient's own cells. In a process developed by Dr. Atala [of Wake University], the patient's cells were grown in a lab, and then seeded on a biodegradable bladder-shaped scaffold.

• Eight weeks later, with the scaffold infused with millions of regrown cells, it was transplanted into the patient. When the scaffold dissolves, Dr. Shenot says, what's left will be a new, functioning organ. (CBS article by Wyatt Anderson)


• Corporate America, meanwhile, already believes regeneration will work. Investment capital has been pouring in to commercialize and mass produce custom-made body parts.

• The Tengion Company has bought the license, built the factory, and is already making those bladders developed at Wake Forest that we told you about earlier.


• "We're actually building a very real business around a very real and compelling patient need," said Dr. Steven Nichtberger, Tengion's CEO.

• Tengion believes regeneration will soon revolutionize transplant medicine. Transplant patients, instead of waiting years for a donated organ, will ship cells off to a lab and wait a few weeks to have their own re-grown.


• "I look at the patients who are on the waitlist for transplant," said Nichtberger. "I look at the opportunity we have to build bladders, to build vessels, to build kidneys. In regenerative medicine, I think it is similar to the semi-conductor industry of the 1980s, you don't know where it's going to go, but you know it's big.“(http://www.cbsnews.com/news/medicines-cutting-edge-re-growing-organs/)



The heart of the matter (1 of 6)

• http://www.nature.com/news/tissue-engineering-how-to-build-a-heart-1.13327

• ( 5 min. video from 2013 article)


• Doris Taylor (director of regenerative medicine research at the Texas Heart Institute in Houston doesn't take it as an insult when people call her Dr Frankenstein. “It was actually one of the bigger compliments I've gotten,” she says — an affirmation that her research is pushing the boundaries of the possible.) She regularly harvests organs such as hearts and lungs from the newly dead, re-engineers them starting from the cells and attempts to bring them back to life in the hope that they might beat or breathe again in the living.


• The strategy is simple enough in principle. • First remove all the cells from a dead organ, it

does not even have to be from a human [decellularize]

• then take the protein scaffold left behind and repopulate it with stem cells immunologically matched to the patient in need [recellularize]


• Success with hollow organs (tracheas & bladders)

• Problems with solid organs :– growing solid organs such as kidneys or lungs

means getting dozens of cell types into exactly the right positions

– simultaneously growing complete networks of blood vessels to keep them alive


– new organs must be sterile– able to grow if the patient is young, – and at least nominally able to repair themselves. – most importantly, they have to work — ideally, for

a lifetime.


• The heart is the third most needed organ after the kidney and the liver, with a waiting list of about 3,500 in the United States alone,

• but it poses extra challenges for transplantation and bioengineering.

• The heart must beat constantly to pump some 7,000 litres of blood per day without a back-up.

• http://www.nature.com/news/tissue-engineering-how-to-build-a-heart-1.13327

2011 state-of-the-art heart rebuilding project

• http://channel.nationalgeographic.com/channel/explorer/videos/the-re-animator/ (3 mins. 27 secs.)

http://channel.nationalgeographic.com/channel/explorer/videos/the-re-animator/

http://channel.nationalgeographic.com/channel/explorer/videos/the-re-animator/

2013 heart research (1 of 3)

• Decellularized mouse heart beats again after regenerating with human heart precursor cells (University of Pittsburgh researchers)

• http://www.sciencedaily.com/releases/2013/08/130813112301.htm


• After 20 days of perfusion, the engineered heart tissues exhibit spontaneous contractions, generate mechanical force and are responsive to drugs. In addition, we observe that heart extracellular matrix promoted cardiomyocyte proliferation, differentiation and myofilament formation from the repopulated human multipotential cardiovascular progenitor cells.


• Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells by

• Tung-Ying Lu• Bo Lin• Jong Kim• Mara Sullivan• Kimimasa Tobita• Guy Salams• & Lei Yang• http://www.nature.com/ncomms/2013/130813/ncomms3307/

full/ncomms3307.html

All about skin

• http://channel.nationalgeographic.com/channel/explorer/videos/the-skin-gun/

• Jorg Gerlach and his skin cell gun (3 mins. 30 secs.)

http://channel.nationalgeographic.com/channel/explorer/videos/the-skin-gun/

http://channel.nationalgeographic.com/channel/explorer/videos/the-skin-gun/

Feb. 2014 update on skin cell gun (1 of 4)

• Question on Reddit (Feb. 2014) : What happened to the skin gun?

• I actually work with in the Skin Gun Lab. It is true that not much press has come out since the National Geographic video. But we are still working with it and improving the process. We are still having occasional clinical trials and are working on getting FDA approval for the gun. I'm not sure what Kinds [sic] of specifics I can tell for legal reasons, but if you have specific questions I can try to answer them.


• In addition, I'd like to say clarify something that bugs me about the national geographic video.

• The police officer and narrator talk as if his wound was completely healed after 4 days. And this is not technically correct. The term that would be appropriate is that the wound was "re-epithelialized" which means that the wound has a thin layer of skin over it and is "dry." yet that layer of skin is extremely thin like paper and very fragile.


• it takes weeks maybe months before the area is "completely" healed.

• "re-epithelialization" in 4 days on a 2nd degree burn is quite good. those burns can take 2 weeks to heal on their own. depending on the depth of the burn. But to say the wound is completely healed in 4 days is not true.


• I truly believe in the technology, but it should not be seen as a miracle, but rather an alternative to mesh grafting that leaves less scarring and can treat areas such as hands and face where mesh grafting is not possible. The analogy I love to use is that a mesh graft is similar to using sod and the skin gun is using grass seed. Hopefully as more research is done the process improves even on patients with less than optimal health.

• http://www.reddit.com/r/askscience/comments/1y2e1r/what_happened_to_the_skin_gun/

How to build a beating heart

• https://www.knowledge.ca/program/national-geographic-specials-how-build-beating-heart– Ear– Heart– Skin cell gun– And more

https://www.knowledge.ca/program/national-geographic-specials-how-build-beating-heart

https://www.knowledge.ca/program/national-geographic-specials-how-build-beating-heart

A return to the eye (1 of 6)

• Hope for blind as scientists find stem cell reservoir in human eye

• (Oct. 1, 2014 article for The Telegraph; http://www.telegraph.co.uk/science/science-news/11133622/Hope-for-blind-as-scientists-find-stem-cell-reservoir-in-human-eye.html)

Stem cells and the eye (2 of 6)

• Researchers at the University of Southampton have discovered a reservoir of stem cells in an area of the eye called the corneal limbus.

• And they have proven that, in the right environment, they can be transformed into photo-receptor cells which react to light.


• And researchers were amazed to find that the cells even existed in the eyes of a 97-year-old, opening up the possibility that the treatment could work for the elderly.


• University of Southampton: Centre for Human Development, Stem Cells and Regeneration

• (http://www.southampton.ac.uk/chdscr/research/retinal_repair.page)

http://www.southampton.ac.uk/chdscr/research/retinal_repair.page

http://www.southampton.ac.uk/chdscr/research/retinal_repair.page


• Degenerative retinal diseases are the leading cause of untreatable blindness worldwide. There is currently no treatment for loss of light sensitive retinal cells (photoreceptors) or the cells which support their function known as retinal pigment epithelium (RPE) cells. Therefore cell based therapies are an attractive treatment option. We are interested in utilising stem cells, as potential cell sources for ocular transplantation.


• Our work includes isolating adult stem cells from the anterior eye, as well as other sources such as induced pluripotent stem cells. We then promote transdifferentiation towards retinal phenotypes including photoreceptor and RPE cells.

• Paper: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0108418 (Adult Limbal Neurosphere Cells: A Potential Autologous Cell Resource for Retinal Cell Generation)

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108418

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108418

Cells: immortal and stem (1 of 16)

• An immortalized cell – proliferates indefinitely– can be naturally occurring or it could have been

induced experimentally.• A cell becomes immortal due to a mutation


• There are various immortal cell lines. – Some are normal cell lines - e.g. derived from

stem cells – Other immortalised cell lines are the in vitro

equivalent of cancerous cells


• Cancer occurs when a somatic cell which normally cannot divide undergoes mutations that de-regulate the normal cell cycle controls and lead to uncontrolled proliferation

• Immortalised cell lines have undergone similar mutations allowing a cell type which would normally not be able to divide to be proliferated in vitro


• The origins of some immortal cell lines, for example HeLa human cells, are from naturally occurring cancers.

• http://en.wikipedia.org/wiki/Immortalised_cell_line


• HeLa cells originated from a sample of cervical cancer taken from Henrietta Lacks in 1951.[

• These cells have been and still are widely used in biological research such as creation of the polio vaccine, sex hormone steroid research, and cell metabolism.

• http://en.wikipedia.org/wiki/Biological_immortality


• Stem cells can also be described as immortal although there is a distinction to be made between these and cell lines such as HeLa which are immortal due to a mutation.


• Two important characteristics of stem cells– they are undifferentiated (not skin, not kidney, not

anything) ... In short, they have the potential to become any kind of cell (pluripotent)

– They are capable of renewing themselves through cell division, sometimes after long periods of inactivity


• Two kinds of stem cells– embryonic stem cells and – non-embryonic "somatic" or "adult" stem cells

which can induced to become pluripotent stem cells (iPSCs)


• In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells.

• hematopoietic stem cells, form all the types of blood cells in the body.

• A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), … make up a small proportion of the stromal cell population in the bone marrow and can generate bone, cartilage, and fat cells that support the formation of blood and fibrous connective tissue. (http://stemcells.nih.gov/info/basics/pages/basics4.asp)


• Like all stem cells, HSCs can replenish all blood cell types (Multipotency) and self-renew.

• It is known that a small number of HSCs can expand to generate a very large number of daughter HSCs. This phenomenon is used in bone marrow transplantation

• (http://en.wikipedia.org/wiki/Hematopoietic_stem_cell)


• One major difference between adult and embryonic stem cells is their different abilities in the number and type of differentiated cell types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin.


• Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells.

• http://stemcells.nih.gov/info/basics/pages/basics10.aspx


• The major concern with the potential clinical application of iPSCs is their propensity to form tumors. Much the same as ESC (embryonic stem cells), iPSCs readily form teratoma when injected into immunodeficient mice. Teratoma formation is considered a major obstacle to stem-cell based regenerative medicine by the FDA.

• (http://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell)


• Germ cells– can be considered immortal

• A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. (http://en.wikipedia.org/wiki/Germ_cell)

Primitive streak (15 of 16)

• The primitive streak in developmental biology refers to the first cells which hint at structure in the embryonic stage for avians, reptiles, and mammals.

• It’s also a collaboration between two sisters: a fashion designer and a developmental biologist

• (http://www.frogheart.ca/?p=3756)

Primitive streak (16 of 16)

Barcoding stem cells

• A 7-year-project to develop a barcoding and tracking system for tissue stem cells has revealed previously unrecognized features of normal blood production … surprisingly, that the billions of blood cells that we produce each day are made not by blood stem cells, but rather their less pluripotent descendants, called progenitor cells

• http://www.eurekalert.org/pub_releases/2014-10/hu-sdb100314.php

• http://phys.org/news/2014-10-barcoding-tool-stem-cells-technology.html

http://www.eurekalert.org/pub_releases/2014-10/hu-sdb100314.php



Organ-on-a-chip preface (1 of 3)

• In silico• In vivo• In vitro• Ex vivo

(http://www.researchgate.net/post/What_is_the_difference_between_Ex_vivo_and_In_vitro)

• Human clinical trials (as opposed to human trials, e.g. Tekmira and ebola)


• Why add a new method?• Why organ-on-a-chip?


• Definition: An organ-on-a-chip ... is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems. ... One day, they will perhaps abolish the need for animals in drug development and toxin testing. (https://en.wikipedia.org/wiki/Organ-on-a-chip)

Organ-on-a-chip (1 of 9)

• The term “Organ-on-a-chip” is used for a cell culture-based model system which mimics (“models”) the smallest functional subunit of an organ or tissue, like the alveolus of a lung or a small number of synchronously contracting heart cells.


• While cells are conventionally cultured in a culture flask or dish in an incubator, in the Organ-on-Chip concept they are cultured inside a so-called “chip”.

• This chip would not be a microprocessor or integrated circuit such as on bank card However, it can actually have been made using the same type of microfabrication process in a clean room.


• The “chip” provides the basic housing for the cells which will form the tissue or organ model. As such it replaces the conventional culture dish.

• Chip is roughly the size of a microscope slide– contains one or more closed chambers– these chambers contain cells which multiply or

differentiate depending on the research• Chip is made of a transparent material for

viewing through a microscope


• The chambers on a chip (microchambers) can have surfaces with different characteristics– e.g., very thin, flexible and stretchable, similar to a

membrane (thickness in the range of microns for example), they are non-toxic for the cells, allow passage of, for example, oxygen or nutrients

– surface can be patterned, or for example designed to contain pores of a defined diameter – all from nanometer to micrometer sized.


– The surface can also be coated with extracellular matrix proteins, these are proteins that normally reside in the intercellular space of tissues and form structures which help create the tissue architecture, and also influence the functions of cells attached to the extracellular matrix molecules.

– The surface patterns can be used to guide the cultured cells in a certain spatial direction.

• (http://www.medicaldelta.nl/uploads/media_items/organ-on-a-chip-information.original.pdf)


• Two organs-on-a-chip (from TissUse):• http://www.youtube.com/watch?v=whsqNvj9

vdU• Images & description of ‘two organs’:

http://www.tissuse.com/technology.html

• TissUse (Uwe Marx claims they have four organs-on-a-chip)

http://www.youtube.com/watch?v=whsqNvj9vdU

http://www.youtube.com/watch?v=whsqNvj9vdU

http://www.tissuse.com/technology.html


• TissUse is a Berlin, Germany-based, vibrant growth company providing high-value services in the area of tissue culture analysis of drug candidates, cosmetics, chemicals and consumer products. TissUse’s proprietary technology platform comprises a number of miniature organ-like structures faithful to their full-size counterparts and connected to one another either by microchannels or by vasculature.


• TissUse launched its Two-Tissue-Culture Chip in 2013. The platform has been successfully applied in more than 20 academic and industrial research projects. The potential commercial applications for TissUse’s proprietary micro-organoid technology are very broad.


• TissUse is a 2010 spinout from the Technische Universität Berlin. On site, more than 20 researchers further develop the Multi-Organ-Chip technology.

• Uwe Marx one of the first to research organ-on-a-chip ... started in early 1990s (according to 9th World Congress on Alternatives to Animal Testing)

Americans and the organ-on-a-chip (1 of 4)

• Don Ingber, the founding director of Harvard’s Wyss Institute for Biologically Inspired Engineering: drugs of the future won’t be tested on rodents with pink noses and whiskers; they’ll be tested on pliable strips of tissue-infused silicon which are less than human in appearance but surprisingly human in function

• A paper that Ingber co-authored in 1994, “Engineering Cell Shape and Function,” laid the foundation for this technology.


• Organs-on-a-chip have already proven to be a more effective tool than mice in some cases: Ingber’s lung-on-a-chip, for example, illuminated a previously unknown connection between the human immune system and pulmonary edema, while another group from the University of California, Irvine, replicated human vasculature for insights into tumor metastasis and environmental-chemical toxicity.


• the final goal, which is to link the micro-organs together and monitor their interactions—resulting in the body-on-a-chip, as the European Union grandly puts it.

• DARPA and the N.I.H. have posted a call, backed with a hundred and forty million dollars, for a network of ten “plug-and-play” organs that survive for four weeks and can, like Legos, be easily rearranged in different orders.


• Only a handful of labs worldwide have so far constructed a system with more than one organ, but such an innovation could be realized in its most basic form by 2017.

• http://www.newyorker.com/tech/elements/of-mice-and-micro-organs

Organ-on-a-chip race (1 of 7)

• Uwe Marx claimed they will have a human-on-a-chip, i.e., 10 organs in 2017 at the 9th World Congress

• US research team (Dan Tagle, leader) claimed the same thing at the congress


• Tagle is associate director of the US National Center for Advancing Translational Sciences

• Team working on ‘chip’ includes researchers from US Food and Drug Administration (FDA) and the US military’s research and development wing, DARPA, and 14 or so universities

• Tagle: 'animal models' are only typically 30% to 60% predictive of human responses to new drugs.


• What might work wonderfully for a rat in the lab won’t necessarily agree with the biology of a human being, and, on the other hand, the perfect drug for humans might never make it past the initial testing stages because it predicts the wrong response in a lab rabbit.


• The team (Tagle’s) has just this week launched a new start-up called Emulate, whose job it is to get this organ-on-a-chip ready for the market.

• http://www.sciencealert.com/news/20143007-25950.html (July 2014)

• http://www.fastcoexist.com/3033574/the-coming-human-body-on-a-chip-that-will-change-how-we-make-drugs?partner=rss

http://www.sciencealert.com/news/20143007-25950.html




• Part of Tagle’s team?• With a new $5.8 million, three-year award

from the National Institutes of Health (NIH), researchers at the University of Pittsburgh School of Medicine will further develop a state-of-the-art, microfluidic 3D model system that mimics structure and function of the liver to better predict organ physiology, assess drug toxicity and build disease models.


• Fifteen NIH Institutes and Centers are involved in the coordination of the tissue chip program. Current funding is being provided by the National Center for Advancing Translational Sciences, the National Institute for Biomedical Imaging and Bioengineering, the National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, NIH Common Fund and NIH Office of Research on Women's Health.


• Collaborators include Martin Yarmush, M.D., Ph.D., of Massachusetts General Hospital; John Wikswo, Ph.D., of Vanderbilt University; Jonathan Himmelfarb, M.D., of the University of Washington; Mark Donowitz, M.D., of Johns Hopkins University; and Mary Estes, Ph.D., of Baylor University.

• http://www.azonano.com/news.aspx?newsID=31154 (Sept. 25, 2014)

http://www.azonano.com/news.aspx?newsID=31154

http://www.azonano.com/news.aspx?newsID=31154

Heart-disease-on-a-chip ( 1 of 4)

• Harvard scientists have merged stem cell and “organ-on-a-chip” technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease.

Heart-disease-on-a-chip (2 of 4)

• Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.


• The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried the patients’ TAZ mutations.


• Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimicked their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart.

• http://news.harvard.edu/gazette/story/2014/05/heart-disease-on-a-chip/

Malaria testing on mice

• “Testing the vaccine’s efficacy was difficult because the parasite that causes malaria in humans only grows in humans,” Lanar says. “But we developed a little trick. We took a mouse malaria parasite and put in its DNA a piece of DNA from the human malaria parasite that we wanted our vaccine to attack. That allowed us to conduct inexpensive mouse studies to test the vaccine before going to expensive human trials.” (http://www.frogheart.ca/?p=14521 posted in Sept. 2014; research from April 2014)


Hanging drop culture (1 of 2)

• Another testing method (3D cell culture):– The hanging drop tissue culture is a technique

utilized in embryology and other fields to allow growth that would otherwise be restricted by the flat plane of culture dishes

– and also to minimize the surface area to volume ratio, slowing evaporation.

Hanging drop culture (2 of 2)

• The classic hanging drop culture is a small drop of liquid, such as plasma or some other media allowing tissue growth, suspended from an inverted watch glass.

• The hanging drop is then suspended by gravity and surface tension, rather than spreading across a plate. This allows tissues or other cell types to be examined without being squashed against a dish.

• (http://embryo.asu.edu/pages/hanging-drop-tissue-culture#sthash.DMtfMVAR.dpuf)

Commercialization happens everywhere

• Centre for Commercialization of Regenerative Medicine

• http://www.ccrm.ca/• Canadian

http://www.ccrm.ca/

http://www.ccrm.ca/

Bits & pieces (1 of 9)

• March 2013, European Union banned cosmetics tested on animals (http://www.crueltyfreeinternational.org/en/the-solution/animal-testing-for-cosmetics-in-europe-finally-set-to-end)

• China ends mandatory testing of cosmetics on animals (http://www.care2.com/causes/its-official-china-ends-mandatory-animal-testing-for-cosmetics.html)


• Seurat-1• http://www.seurat-1.eu/• This FP7 Research Initiative was created through a call

for proposals by the European Commission that was published in June 2009. The Cosmetics Europe industry offered to match the European Commission’s funds to make a total of EUR 50 million available to try to fill current gaps in scientific knowledge and accelerate the development of non-animal test methods. [Full disclosure: Seurat-1 flew me to the 9th World Congress in Prague)

http://www.seurat-1.eu/


• The practice of ‘guinea-pigging’


• September 11, 2001, James Rockwell was camped out in a clinical-research unit on the eleventh floor of a Philadelphia hospital, where he had enrolled as a subject in a high-paying drug study. As a rule, studies that involve invasive medical procedures are more lucrative—the more uncomfortable, the better the pay—and in this study subjects had a fibre-optic tube inserted in their mouths and down their esophaguses so that researchers could examine their gastrointestinal tracts.


• Rockwell is a wiry thirty-year-old massage-therapy student with a pierced nose; he seems to bounce in his seat as he speaks, radiating enthusiasm. Over the years, he estimates, he has enrolled in more than twenty studies for money. The Philadelphia area offers plenty of opportunities for aspiring human subjects. It is home to four medical schools and is part of a drug-industry corridor that stretches into New Jersey. Bristol-Myers Squibb regularly sends a van to pick up volunteers at the Trenton train station.


• from subject recruitment and testing through F.D.A. approval. Speed is critical: a patent lasts twenty years, and a drug company’s aim is to get the drug on the shelves as early in the life of the patent as possible.

• Guinea-pigging takes place in US and elsewhere


• The most notorious recent disaster for healthy volunteers took place in March, 2006, [article written in 2008] at a testing site run by Parexel at Northwick Park Hospital, outside London; subjects were offered two thousand pounds to enroll in a Phase I trial of a monoclonal antibody, a prospective treatment for rheumatoid arthritis and multiple sclerosis.


• Six of the volunteers had to be rushed to a nearby intensive-care unit after suffering life-threatening reactions—severe inflammation, organ failure. They were hospitalized for weeks, and one subject’s fingers and toes were amputated. All the subjects have reportedly been left with long-term disabilities.


• http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging



Date post:	05-Jan-2016
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